Acne Solution

ABSTRACT

A composition for the treatment of acne includes hydrolyzed  Psoralea Corylifolia , containing a component bakuchiol, is solubilized in a water-based solution. The composition is for topical application to the skin. In a specific implementation, the composition is a water-based acne gel. In a specific implementation, a composition includes Bakutrol™, which includes bakuchiol, and bisabolol. The composition can include a polysorbate surfactant. In implementations, these ingredients are combined with other active ingredients, including for example, salicylic acid. A process of preparation of the composition allows for the stabilization of Bakutrol in solution.

BACKGROUND OF THE INVENTION

The invention relates to the field of skincare compositions and morespecifically to compositions for treating acne vulgaris.

Acne vulgaris (acne) is a chronic inflammatory condition of thepilosebaceous units of the skin, which is particularly prevalent inadolescents. The condition generally causes the formation, on the skin,of comedones, red papules, pustules and sometimes cysts. This isunsightly and furthermore, if untreated, acne can lead to scarring ofthe skin. The major causes of acne are thought to be an increase insebum production, an increased presence of Proprionibacterium acnes (P.acne), blockage of the pilosebaceus duct and the production ofinflammation.

Typical treatments for acne include therapies containing benzoylperoxide, retinoids or a combination of an antibiotic and benzoylperoxide. However, these therapies are harsh on the skin and can causeexcessive dryness, redness, irritation, and peeling. These therapies cantake between 3 to 6 weeks to reduce inflammatory acne lesions by fiftypercent. The amount of time its takes for typical acne treatmentproducts to work and the tolerability issues they present, cause usersto be non-compliant in using these products as prescribed; experiencelittle to no reduction in acne; and be less likely to re-purchase theacne products.

There is a continuing demand for acne treatment therapies that are moreeffective and potent, and easy to use, while minimizing harsh sideeffects on the skin. Therefore, there is a need for improved treatmentproducts for acne.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to a composition and process ofpreparation of a compound for the treatment of acne. The compound is fortopical application to the skin. Specifically, the composition includesBakutrol™, containing the ingredient bakuchiol, that is solubilized in awater-based solution.

In a specific implementation, a composition includes hydrolyzed PsoraleaCorylifolia containing bakuchiol as a primary component (or Bakutrol),and bisabolol. The composition can include a preservative, a surfactant,an emollient, or a combination. In a specific implementation, Bakutroland bisabolol RAC are combined with polysorbate 20 as the preservative.In implementations, these ingredients are combined with other activeingredients, including for example, salicylic acid.

In a specific implementation, a composition includes Bakutrol,bisabolol, polysorbate 20, and other ingredients: salicylic acid, oleaeuropaea (olive) fruit extract, perilla ocymoides leaf extract (e.g.,shiso extract powder), sodium PCA, hydroxyethylcellulose, disodium EDTA,gluconolactone, lactic acid, sodium benzoate, dextrin, water, glycolicacid, sodium hydroxide, and butylene glycol. In other implementations,the composition can include Bakutrol and any one or more of theingredients, in any combination.

The present invention includes a method of preparation of a water-basedacne gel composition. The preparation solubilizes Bakutrol which allowsit to be effectively absorbed by the skin, and allows it to be stable inthe gel. The gel is effective in reducing inflammatory acne lesions by50 percent in as few as about 7 days with a 90 percent reductionachieved in about 14 days. Unlike typical prescription andover-the-counter acne treatments, the gel does not cause collateraldamage to the skin, including dry skin, skin irritation, redness, andpeeling.

Other objects, features, and advantages of the present invention willbecome apparent upon consideration of the following detailed descriptionand the accompanying drawings, in which like reference designationsrepresent like features throughout the figures.

DETAILED DESCRIPTION OF THE INVENTION

Acne is a common skin condition, characterized by areas of skin withseborrhea (scaly red skin), comedones (blackheads and whiteheads),papules (pinheads), pustules (pimples), nodules (large papules) andpossibly scarring.

Approximately 650 million people worldwide, or about 9.4 percent of theworld population, experience some degree of acne. In the United Statesalone, acne affects about 40 to 50 million people annually. Research hasshown that about 85% of young people between the ages of 12 and 24 yearshave acne, and while it is most common in teenagers, acne affects 8percent of adults aged 25 to 34 years and 3 percent of adults aged 35 to44 years.

Modern societies place a great emphasis on physical appearance. Althoughacne is not a life-threatening condition, it has significant physicaland psychological ramifications such as permanent scarring, poor selfimage and self esteem, social phobia, social dysfunction, depression,anxiety, suicide, and overall reduced quality of life. Therefore, acneshould be regarded as a serious medical disorder.

The available topical agents for the treatment of acne typically includebenzoyl peroxide, retinoids, antibiotics, antiseborrheic medications,antiandrogen medications, hormonal treatments, salicylic acid, alphahydroxy acid, and a combination of these. The therapeutic success inacne of these treatments is highly dependent on a regular application ofthe topical agents over a prolonged period of time. However,disadvantages associated with these commonly used topical agentsconsiderably affect patient compliance and obstruct the treatment. Theseagents can cause undesirable side effects such as excessive dryness,redness, irritation and peeling. In addition, the use of antibiotics haslimitations due to development of resistance by bacteria. The use ofretinoids has also been linked to causing developmental malformations.

These agents can take long periods of time to work. Research has shownthat even effective prescription and over-the-counter acne treatmentproducts can take up to between 3 to 6 weeks to reduce inflammatory acnelesions by about 50 percent. These and other disadvantages can causeusers to be non-compliant in using acne products as prescribed.

Bakutrol™ is an antimicrobial and anti-inflammatory agent that has beenshown to help reduce the bacterial activity, inflammation, and scarringseen in acne. Bakutrol is a trademark of Unigen, Inc. Any trademarkslisted in this patent application are the property of their respectiveowners. Bakutrol is a natural, botanical agent. It contains bakuchiol, anatural phenol isolated from the seeds of Psoralea corylifolia orPsoralea glandulosa, a tree native to China known for its uses intraditional Chinese medicine.

Bakuchiol has a natural ability to fight inflammation, by controllingleukocytic functions at the site of the inflammation. In clinicalstudies, Bakutrol reduced both inflammatory and non-inflammatory acnelesions without the adverse side effects often found with harshchemicals. Bakuchiol also possesses protective antioxidantcharacteristics due to its scavenging activity against oxidative damageto lipids and proteins. Additionally, Bakutrol significantly reducesscarring or Post-Inflammatory Hyperpigmentation (PIH), the dark spotsleft behind long after the acne lesion has healed. Unlike traditionalacne treatments, Bakutrol has been clinically proven to reduce PIH. Instudies, bakuchiol has been shown to be more potent at treating acnethan benzoyl peroxide.

Research on bakuchiol demonstrates its ability to inhibit both thegrowth of acne-causing bacteria and the COX/LOX inflammatory pathways.Bakuchiol has also been shown to regulate sebum production. A pilotstudy on subjects with a diagnosis of facial acne vulgaris showedsignificant reductions in inflammatory (papules, cysts) andnon-inflammatory (blackheads) lesions (Yaping, E, et al, SUNY DownstateMedical Center, Brooklyn, N.Y.). Forty-five percent of these studysubjects also experienced partial or total clearing of acne-relatedpost-inflammatory hyperpigmentation (PIH) which can follow acne vulgarisand results in skin melanosis (dark pigmentation).

Hydrolyzed Psoralea Corylifolia, containing bakuchiol, is naturallyinsoluble in water. The hydrolysis of Psoralea Corylifolia extracts thecomponent bakuchiol, which is contained in Bakutrol. It is verydifficult to incorporate Bakutrol into a water-based gel preparation fortopical use since it is insoluble. Some prescription andover-the-counter acne products contain suspended particles of bakuchiolthat are very large and cannot penetrate into sebaceous follicles(pores). The skin cannot absorb these products even when excess amountsof bakuchiol are present. These products are therefore, ineffective atdelivering bakuchiol to the dermal tissue. Furthermore, due tobakuchiol's inability to solubilize in water, bakuchiol can becomeunstable in aqueous solutions.

The present invention uses novel technology including a uniqueformulation and preparation that solubilizes bakuchiol (Bakutrol),without the use of alcohol. When Bakutrol is solubilized, it can beeffectively delivered into the sebaceous follicles (pores) withbisabolol where these ingredients, with salicylic acid, can promoterapid clinical results. Solubilized Bakutrol can be easily absorbed bythe skin. Hence, the skin treatment properties of Bakutrol aresignificantly enhanced when it is solubilized according to the presentinvention.

Bisabolol is the main active ingredient of the medical plant chamomile(Matricaria chamomilla). Bisabolol protects and heals the skin from theeffects of daily stress. It is a naturally occurring active ingredientthat accelerates the healing process of skin. Research has shown that itcontains anti-inflammatory properties.

In a specific implementation, a composition includes hydrolyzed PsoraleaCorylifolia, containing bakuchiol as its primary component (or Bakutrol)and bisabolol. The composition can include a polysorbate surfactant,which is a stable and relatively nontoxic agent that allows it to beused as a detergent and emulsifier in a number of domestic, scientific,and pharmacological applications. In pharmaceutical applications, it isused to stabilize emulsions and suspensions. In a specificimplementation, Bakutrol and bisabolol RAC is combined with polysorbate20 as the emollient.

In a specific implementation, a composition includes Bakutrol,bisabolol, polysorbate 20, and other ingredients: salicylic acid, oleaeuropaea (olive) fruit extract, perilla ocymoides leaf extract (e.g.,shiso extract powder), sodium PCA, hydroxyethylcellulose, disodium EDTA,gluconolactone, lactic acid, sodium benzoate, dextrin, water, glycolicacid, sodium hydroxide, and butylene glycol. In other implementations,the composition can include Bakutrol and any one or more of theingredients, in any combination. Other ingredients (and theirequivalents) can be substituted for or replace any of the one or more ofthe listed ingredients. For example, polysorbate 20 can be replaced bycaprylyl glycol, ethylhexylglycerin, or PPG-2 isoceteth-20 acetate.

Research has shown that there is a synergistic effect in solubilizingBakutrol, rather than an additive effect, when combinations of theingredients listed above are combined. In a mixture of ingredients, eachingredient works through a specific mechanism of action, and has anindividual effect when combined with Bakutrol. An additive effect of themixture is the same as the sum of the individual effects of eachingredient. In contrast, a synergistic effect of a mixture of substancesis greater than the sum of the individual effects. For example,Compounds A and B each has a solubility rate of 10 percent when usedindividually. However in combination, the actual combined solublity rateis 30 percent, rather than an anticipated additive effect of 20 percent,resulting in an enhancement of 10 percent. The combinations ofingredients, such as those presented above, have been shown to producethis synergistic effect. In combination, the solubility of Bakutrol isamplified. Consequently, the combination of ingredients can be effectivein solubilizing and stabilizing Bakutrol, while optimizing the benefitsof Bakutrol, and can increase the duration of time of stability of theBakutrol in a gel solution.

In these implementations, Bakutrol can be solubilized to allow for acomposition with enhanced acne treatment properties. As discussed above,when Bakutrol is solubilized, it can be effectively be absorbed into theskin to treat the skin. Research has shown that in a specificimplementation of the composition, the product (a water-based acne gel),after applied to users' acne areas over several weeks, reducedinflammatory acne lesions by 50 percent in about 7 days with a 90percent reduction achieved in 14 days. The product was also seen to workabout three times faster than typical prescription and over-the-counteracne products. The results showed that the product does not causecollateral damage to the skin, including dry skin, skin irritation,redness, and peeling.

In these implementations, Bakutrol is stable in the product, whileretaining its acne treatment properties. Some accelerated stabilitystudies show that the product is stable for about one month to about 3months at 25 degrees Celsius, 4 degrees Celsius, and 40 degrees Celsius,with no separation or precipitation. This correlates to about an 8 monthto about 24 months shelf life.

The composition in these implementations is not limited to the specificingredients presented. A composition of the invention may haveadditional compounds (not necessarily described in this application),different compounds which replace some of the compounds presented, fewerof the compounds presented, or any combination of these. For example,Bakutrol and bisabolol can be combined with other active ingredients(not presented above) such as benzoyl peroxide, retinoids (e.g., retinoland tretinoin), and antibiotics (e.g., erythromycin, clindamycin, andtetracycline), and the remainder is an emollient, water and othersolvents. In these implementations, various ingredients other than thosepresented above can be used in combination with Bakutrol (e.g., othersolvents such as caprylyl glycol, ethylhexylglycerin, PPG-2 isoceteth-20acetate, and others).

Table A below provides the range of amount (percentage by weight) ofeach ingredient that can be used, while still maintaining its efficacyas an acne treatment agent. It should be understood that the inventionis not limited to the specific percentages presented. A formulation ofthe invention may have additional compounds (not necessarily describedin this application), different compounds which replace some of thecompounds presented, fewer of the compounds presented, or anycombination of these. Further, the compounds in other implementations ofthe invention may not be exactly the same as the compounds presented andmay be modified or altered as appropriate for a particular applicationor based on the data or situation. For example, the percentages can alsobe specified by volume.

TABLE A Range (Percentage by Weight Item Number Ingredient (% WT/WT))  1Deionized Water 40.00-80.00  2 Hydroxyethylcellulose, Sodium 0.10-5.00Nitrate, Water (Natrosol 250 HHX Pharm)  3 Disodium EDTA (Dissolvine Na-0.01-1.00 2-P)  4 Sodium PCA, Water (Nalidone) 0.10-5.00  5 ButyleneGlycol (1,3-Butylene 0.10-5.00 Glycol)  6 Salicylic Acid (Curcylic SA100) 0.10-5.00  7 Glycolic Acid, Water (Glypure 10.00-20.00 70)  8Lactic Acid, Water (Purac 0.10-5.00 HiPure 90)  9 Deionized Water 5.00-15.00 10 Sodium Hydroxide (Sodium 1.00-5.00 Hydroxide, Pellets,NF) 11 Deionized Water 0.10-5.00 12 Dextrin, Perilla Ocymoides Leaf0.01-1.00 extract (Shiso Extract Powder) 13 Deionized Water 0.10-5.00 14Olea Europaea Fruit Extract, 0.01-1.00 Water (EurolBT) 15Gluconolactone, Sodium 0.10-5.00 Benzoate (Geogard Ultra) 16 Polysorbate20 (Tween-20-LQ- 1.00-5.00 (AP)) 17 Hydrolyzed Psoralea Corylifolia0.01-1.00 Extract (Bakutrol(TM)) 18A Bisabolol (Bisabolol RAC) 0.01-1.0018B Caprylyl Glycol (Lexgard O) 0.01-1.00 18C Ethylhexylglycerin(Sensiva SC 0.01-1.00 50) 18D PPG-2 Isoceteth-20 Acetate 0.10-3.00 (CUPLPIC)

In specific implementations, a composition for an acne solution includes0.01 percent to about 1 percent by weight of Bakutrol, and about 0.01percent to about 1 percent by weight of bisabolol RAC. In a specificimplementation, the ratio of Bakutrol to bisabolol RAC is about 12:1,12.8:1 11:1, 11:5:1, 10:1, 10.1:1, 10.2:1 10.5:1, 10.8:1 9:1, 9.5:1,9.7:1, 9.8:1, 9:9:1, 8:1, 8.25:1, or 8.5:1. In other implementations,this ratio can vary. The composition can include a greater amount ofbisabolol than of Bakutrol. In these implementations, the ratio can beabout 1:1, 1:2, 1:4, 1:6, 1:8, or 1:10.

In a specific implementation, the composition includes about 0.01,0.015, 0.02, 0.025, 0.03, 0.035, 0.05, 0.06, 0.07, 0.075, 0.09, 0.1,0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 percent by weightof Bakutrol. Additionally, the composition can include about 0.01,0.015, 0.02, 0.025, 0.03, 0.035, 0.05, 0.06, 0.07, 0.075, 0.09, 0.1,0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 percent ofbisabolol RAC. Bakutrol and bisabolol can be present in any combinationof percentages, either individually or in combination.

Salicylic acid can be included in the composition in a range of about0.10 percent to about 5.0 percent by weight. Salicylic acid is typicallyused to treat skin conditions including acne. The amount salicylic acidcan vary in this range as appropriate for a particular application orbased on the data or situation. In a specific implementation, the ratioof salicylic acid to Bakutrol is about 12:1, 12.8:1 11:1, 11:5:1, 10:1,10.1:1, 10.2:1 10.5:1, 10.8:1 9:1, 9.5:1, 9.7:1, 9.8:1, 9:9:1, 8:1,8.25:1, or 8.5:1. In other implementations, this ratio can vary. Thecomposition can include a greater amount of Bakutrol than of salicylicacid. In these implementations, the ratio can be about 1:1, 1:2, 1:3,1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10. In a specific implementation, thecomposition includes about 0.5, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0,1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.5, 2.0, 2.5, 3.0, 4.0, or5.0 percent by weight of salicylic acid.

In a specific implementation, the composition includes alpha hydroxyacid (AHA). In implementations, alpha hydroxy acid can include one ormore of glycolic acid, lactic acid, malic acid, citric acid, tartaricacid, or suitable mixtures of two or more thereof. In a specificimplementation, the composition includes about 10 percent to about 20percent of glycolic acid, and 0.10 percent to about 5 percent of lacticacid. For example, glycolic acid is present in about 10.5, 11.5, 12.5,13, 13.5, 13.8, 14.0, 14.1, 14.3, 14.5, 14.8, 15.0, 15.3, 15.8, 16.0,16.5, or 17.0 percent, and lactic acid is present in about 0.15, 0.3,0.5, 0.7, 0.75, 0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 2.0, 2.4,2.9, 3.0, 3.5, or 4.0 percent. The amount of this combination of alphahydroxy acids can be included individually or in combination.

The composition can include an extract derived from Perilla Ocymoides inan amount from about 0.01 to about 1.0 percent. For example, the amountof extract is about 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.05, 0.06,0.07, 0.075, 0.09, 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or1.0 percent by weight. In a specific implementation the extract is anextract power from shiso.

The composition can also include an extract derived from the OleaEuropaea fruit, in an amount from about 0.01 to about 1.0 percent. Forexample, the amount of extract is about 0.01, 0.015, 0.02, 0.025, 0.03,0.035, 0.05, 0.06, 0.07, 0.075, 0.09, 0.1, 0.2, 0.25, 0.3, 0.4, 0.5,0.6, 0.7, 0.8, 0.9, or 1.0 percent by weight. The fruit is commonlycalled the olive.

The composition can include hydroxyethylcellulose in an amount fromabout 0.1 to about 5.0 percent. For example, the amount can be about0.15, 0.3, 0.5, 0.7, 0.75, 0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7,2.0, 2.4, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 percent by weight.

Disodium EDTA can be included in an amount from about 0.01 to about 1percent. For example, the amount of disodium EDTA is about 0.01, 0.015,0.02, 0.025, 0.03, 0.035, 0.05, 0.06, 0.07, 0.075, 0.09, 0.1, 0.2, 0.25,0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 percent by weight.

Sodium PCA can be included in an amount from about 0.1 to about 5.0percent. For example, the amount can be about 0.15, 0.3, 0.5, 0.7, 0.75,0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 2.0, 2.4, 2.9, 3.0, 3.5,4.0, 4.5, or 5.0 percent by weight.

The composition can include butylene glycol in an amount from about 0.1to about 5.0 percent. For example, the amount can be about 0.15, 0.3,0.5, 0.7, 0.75, 0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 1.9, 1.95,2.0, 2.05, 2.1, 2.2, 2.3, 2.4, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 percentby weight.

The composition can include sodium hydroxide in an amount from about 0.1to about 5.0 percent. For example, the amount can be about 0.15, 0.3,0.5, 0.7, 0.75, 0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 1.9, 1.95,2.0, 2.05, 2.1, 2.2, 2.3, 2.4, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 percentby weight.

The composition can include sodium benzoate in an amount from about 0.1to about 5.0 percent. For example, the amount can be about 0.15, 0.3,0.5, 0.7, 0.75, 0.8, 0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 1.9, 1.95,2.0, 2.05, 2.1, 2.2, 2.3, 2.4, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 percentby weight. In a specific implementation, the composition includes sodiumbenzoate with gluconolactone.

The composition can include other ingredients including preservatives,thickeners, humectants, stabilizers, buffers, emollients, emulsifyingagents, and water. In a specific implementation, the compositionincludes about 1 percent to about 5 percent by weight of polysorbate 20.For example, an amount of about 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 1.9, 1.95,2.0, 2.05, 2.1, 2.2, 2.3, 2.4, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 percentby weight is included.

In other implementations, polysorbate 20 can be substituted with 0.01percent to about 1 percent of caprylyl glycol. For example, an amount ofabout 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.05, 0.06, 0.07, 0.075,0.09, 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 percentby weight is included. In another specific implementation, caprylylglycol can be substituted with 0.01 percent to about 1 percent ofethylhexylglycerin. For example, an amount of about 0.01, 0.015, 0.02,0.025, 0.03, 0.035, 0.05, 0.06, 0.07, 0.075, 0.09, 0.1, 0.2, 0.25, 0.3,0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 percent by weight is included. Andin yet another specific implementation, ethylhexylglycerin can besubstituted with 0.1 percent to about 3 percent of PPG-2 isoceteth-20acetate. For example, an amount of about 0.15, 0.3, 0.5, 0.7, 0.75, 0.8,0.9, 0.95, 1.0, 1.1, 1.3, 1.4, 1.6, 1.7, 1.9, 1.95, 2.0, 2.05, 2.1, 2.2,2.3, 2.4, 2.9, or 3.0 percent by weight is included. In these otherimplementations, other ingredients' weight by percentage can be adjustedaccordingly. For example, in a composition using 1.00 percent PPG-2isoceteth-20 acetate, an amount of deionized water can be increased ordecreased accordingly.

The amount of water in the final composition can be from about 45 toabout 99 percent. For example, in a specific implementation, deionizedwater is included in an amount of about 70, 70.5, 70.3, 70.9, 72.5,72.9, 73.0, 73.1, 73.3, 73.4, 73.5, 73.6, 73.7, 73.9, 80.1, 80.15, 80.2,or 81.0 percent by weight.

The composition can be formulated as a water-based, topical gel. In aspecific implementation, the gel is a semiviscous gel solution. Thesolution can have a specific gravity from about 1.06 to 1.10, about 17.5percent to about 21.5 percent of solids, a viscosity of about 4000 toabout 8000 centipoise (cps), and a pH of about 3.5 to about 4.5.

The composition can be included in a cleanser, cream, lotion, serum,essence, balm, or an emulsion (e.g., an oil-in-water emulsion or awater-in-oil emulsion). For example, the composition can be included ina group of products (e.g., day cream, night cream, cleanser, toner, andacne gel), prescribed for use together, in order to maximize the acnetreatment properties of the composition. The composition can bealcohol-free or substantially alcohol-free. Formulations can includemore or less humectants, oils, botanicals, or other ingredients wherethe composition is adjusted for different skin types (e.g., dry, oily,acne prone, combination, dull, sensitive, or aging skin).

The present invention includes a method of preparation of a water-basedacne gel composition. The preparation solubilizes Bakutrol and allows itto be stable in the gel.

The procedure listed below in Table B provides a specific example of apreparation of a water-based acne gel including solubilized Bakutrol.The item numbers presented in Table B are the item numbers as presentedin Table A above. The amount of each item is according to the rangespresented in Table A, and in the specific implementations providedabove. It should be understood that the invention is not limited to thespecific percentages presented. A formulation of the invention may haveadditional compounds (not necessarily described in this application),different compounds which replace some of the compounds presented, fewerof the compounds presented, or any combination of these. Further, thecompounds in other implementations of the invention may not be exactlythe same as the compounds presented and may be modified or altered asappropriate for a particular application or based on the data orsituation. For example, the percentages can also be specified by volume.

It should further be understood that the invention is not limited to thespecific steps presented below. A preparation of the invention may haveadditional steps (not necessarily described in this application),different steps which replace some of the steps presented, fewer stepsor a subset of the steps presented, or steps in a different order thanpresented, or any combination of these. Further, the steps in otherimplementations of the invention may not be exactly the same as thesteps presented and may be modified or altered as appropriate for aparticular application or based on the data or situation.

TABLE B Step Number 1 Into a first processing tank, equipped with apropeller mixer and side sweep, add item #1 (deionized water). Beginhigh speed mixing. 2 Sprinkle in item #2. Mix until completely uniformand free of lumps. 3 Heat to 70-75 degrees Celsius. Add item #3 and item#4. Mix until uniform. Cool to 60-65 degrees Celsius. 4 In a separatevessel, add item #5 and item #6. Heat to 60-65 degrees Celsius untiluniform. Add to the first processing tank. Mix until completely uniform.Cool to 55-60 degrees Celsius. 5 Add item #7 and item #8. Mix untiluniform. Cool to 50-55 degrees Celsius. 6 Premix item #9 and item #10.Slowly add to the first processing tank. Mix until uniform. Cool to45-50 degrees Celsius. 7 Premix item #11 and item #12. Add to the firstprocessing tank. Mix until uniform. 8 Premix item #13 and item #14. Addto the first processing tank. Mix until uniform. Cool to 40-45 degreesCelsius. 9 Add item #15. Mix until uniform. 10 Premix item #16, item#17, and item #18A. Add to the first processing tank. Mix untilcompletely uniform. 11 QS batch with deionized water if necessary.Continue mixing and cooling to 35 degrees Celsius.

In another specific implementation, in step 10, item #18A (polysorbate20) can be substituted with an amount of caprylyl glycol (item #18B),while the other steps and ingredients are the same as presented in TableB. In another specific implementation, in step 10, caprylyl glycol canbe substituted with an amount of ethylhexylglycerin (item #18C). And inyet another specific implementation, in step 10, ethylhexylglycerin canbe substituted with an amount of PPG-2 isoceteth-20 acetate (item #18D).In these other implementations, other ingredients' weight by percentagecan be adjusted accordingly. For example, in a composition using 1.0percent PPG-2 isoceteth-20 acetate, an amount of deionized water can bedecreased or increased accordingly.

This description of the invention has been presented for the purposes ofillustration and description. It is not intended to be exhaustive or tolimit the invention to the precise form described, and manymodifications and variations are possible in light of the teachingabove. The embodiments were chosen and described in order to bestexplain the principles of the invention and its practical applications.This description will enable others skilled in the art to best utilizeand practice the invention in various embodiments and with variousmodifications as are suited to a particular use. The scope of theinvention is defined by the following claims.

1-8. (canceled)
 9. A method of preparing an aqueous mixture comprising:mixing deionized water and hydroxyethylcellulose to obtain a firstmixture; applying heat to the first mixture until the first mixturereaches about 75 degrees Celsius; adding disodiumethylenediaminetetraacetic acid (EDTA) and sodium pyrrolidone carboxylicacid (PCA) to the first mixture and mixing to obtain a second mixture;allowing the second mixture to cool to from about 60 to 65 degreesCelsius; mixing butylene glycol and salicylic acid to obtain a thirdmixture; applying heat to the third mixture until the third mixturereaches about 65 degrees Celsius; mixing the third mixture and secondmixture together to obtain a fourth mixture; allowing the fourth mixtureto cool to from about 55 to 60 degrees Celsius; adding glycolic acid andlactic acid to the fourth mixture and mixing to obtain a fifth mixture;allowing the fifth mixture to cool to from about 50 to 55 degreesCelsius; mixing deionized water and sodium hydroxide to obtain a sixthmixture; mixing the sixth mixture and the fifth mixture together toobtain a seventh mixture; allowing the seventh mixture to cool to fromabout 45 to 50 degrees Celsius; mixing deionized water and perillaocymoides leaf extract to obtain an eighth mixture; mixing the eighthmixture and the seventh mixture to obtain a ninth mixture; mixingdeionized water and olea europaea fruit extract to obtain a tenthmixture; mixing the tenth mixture and ninth mixture to obtain aneleventh mixture; allowing the eleventh mixture to cool to from about 40to 45 degrees Celsius; adding sodium benzoate to the eleventh mixtureand mixing to obtain a twelfth mixture; mixing polysorbate 20,bisabolol, and hydrolyzed Psoralea Corylifolia extract to obtain athirteenth mixture; mixing the thirteenth mixture and twelfth mixture toobtain a fourteenth mixture; allowing the fourteenth mixture to cool toabout 35 degrees Celsius; and obtaining an aqueous mixture that is acombination of the twelfth and thirteenth mixtures.
 10. An aqueous acnetreatment formulation comprising the mixture of claim
 9. 11. An aqueousgel formulation comprising the mixture of claim
 9. 12. The aqueous acnetreatment formulation of claim 10 wherein the formulation does notcomprise an oil constituent.
 13. The aqueous gel formulation of claim 11wherein the gel formulation comprises a viscosity of about 4000 to about8000 centipoise.
 14. The method of claim 9 comprising: adding benzoylperoxide to the polysorbate 20, bisabolol, and hydrolyzed PsoraleaCorylifolia extract of the thirteenth mixture.
 15. The method of claim 9wherein the aqueous mixture comprises at least one of a retinoid or anantibiotic.
 16. The method of claim 9 wherein the hydrolyzed PsoraleaCorylifolia extract comprises bakuchiol.
 17. The method of claim 9wherein the aqueous mixture does not comprise an alcohol constituent.18. A method of preparing a water-based mixture comprising: mixingdeionized water and hydroxyethylcellulose to obtain a first mixture;applying heat to the first mixture until the first mixture reaches about75 degrees Celsius; adding disodium ethylenediaminetetraacetic acid(EDTA) and sodium pyrrolidone carboxylic acid (PCA) to the first mixtureand mixing to obtain a second mixture; allowing the second mixture tocool to from about 60 to 65 degrees Celsius; mixing butylene glycol andsalicylic acid to obtain a third mixture; applying heat to the thirdmixture until the third mixture reaches about 65 degrees Celsius; mixingthe third mixture and second mixture together to obtain a fourthmixture; allowing the fourth mixture to cool to from about 55 to 60degrees Celsius; adding glycolic acid and lactic acid to the fourthmixture and mixing to obtain a fifth mixture; allowing the fifth mixtureto cool to from about 50 to 55 degrees Celsius; mixing deionized waterand sodium hydroxide to obtain a sixth mixture; mixing the sixth mixtureand the fifth mixture together to obtain a seventh mixture; allowing theseventh mixture to cool to from about 45 to 50 degrees Celsius; mixingdeionized water and perilla ocymoides leaf extract to obtain an eighthmixture; mixing the eighth mixture and the seventh mixture to obtain aninth mixture; mixing deionized water and olea europaea fruit extract toobtain a tenth mixture; mixing the tenth mixture and ninth mixture toobtain an eleventh mixture; allowing the eleventh mixture to cool tofrom about 40 to 45 degrees Celsius; adding sodium benzoate to theeleventh mixture and mixing to obtain a twelfth mixture; mixingpolysorbate 20, bisabolol, and bakuchiol to obtain a thirteenth mixture;mixing the thirteenth mixture and twelfth mixture to obtain a fourteenthmixture; allowing the fourteenth mixture to cool to about 35 degreesCelsius, and obtaining a water-based mixture that is a combination ofthe twelfth and thirteenth mixtures, wherein the water-based mixturedoes not comprise an oil constituent.
 19. A water-based acne treatmentformulation comprising the mixture of claim
 18. 20. A water-based gelformulation comprising the mixture of claim
 18. 21. The method of claim18 wherein the mixture does not comprise an alcohol constituent.
 22. Themethod of claim 18 wherein a ratio of an amount of bakuchiol to anamount of bisabolol is about 10:1.
 23. The method of claim 18 wherein aratio of an amount of salicylic acid to an amount of bakuchiol is about10:1.
 24. A method of preparing a water-based mixture comprising: mixingdeionized water and hydroxyethylcellulose to obtain a first mixture;applying heat to the first mixture until the first mixture reaches about75 degrees Celsius; adding disodium ethylenediaminetetraacetic acid(EDTA) and sodium pyrrolidone carboxylic acid (PCA) to the first mixtureand mixing to obtain a second mixture; allowing the second mixture tocool to from about 60 to 65 degrees Celsius; mixing butylene glycol andsalicylic acid to obtain a third mixture; applying heat to the thirdmixture until the third mixture reaches about 65 degrees Celsius; mixingthe third mixture and second mixture together to obtain a fourthmixture; allowing the fourth mixture to cool to from about 55 to 60degrees Celsius; adding glycolic acid and lactic acid to the fourthmixture and mixing to obtain a fifth mixture; allowing the fifth mixtureto cool to from about 50 to 55 degrees Celsius; mixing deionized waterand sodium hydroxide to obtain a sixth mixture; mixing the sixth mixtureand the fifth mixture together to obtain a seventh mixture; allowing theseventh mixture to cool to from about 45 to 50 degrees Celsius; mixingdeionized water and perilla ocymoides leaf extract to obtain an eighthmixture; mixing the eighth mixture and the seventh mixture to obtain aninth mixture; mixing deionized water and olea europaea fruit extract toobtain a tenth mixture; mixing the tenth mixture and ninth mixture toobtain an eleventh mixture; allowing the eleventh mixture to cool tofrom about 40 to 45 degrees Celsius; adding sodium benzoate to theeleventh mixture and mixing to obtain a twelfth mixture; mixing a firstcompound, bisabolol, and hydrolyzed Psoralea Corylifolia extract toobtain a thirteenth mixture; mixing the thirteenth mixture and twelfthmixture to obtain a fourteenth mixture; allowing the fourteenth mixtureto cool to about 35 degrees Celsius, and obtaining a water-based mixturethat is a combination of the twelfth and thirteenth mixtures, whereinthe water-based mixture does not comprise an alcohol constituent. 25.The method of claim 24 wherein the first compound comprises polysorbate20.
 26. The method of claim 24 wherein the first compound comprisescaprylyl glycol.
 27. The method of claim 24 wherein the first compoundcomprises ethylhexylglycerin.
 28. The method of claim 24 wherein thefirst compound comprises PPG-2 isoceteth-20 acetate.
 29. The method ofclaim 24 wherein the water-based mixture does not include an oilconstituent.